What are the treatment options for Gout (Gouty Arthritis)?

From the Guidelines

Gout treatment should prioritize urate-lowering therapy (ULT) with allopurinol as the first-line option, starting at a low dose and titrating upwards to achieve a serum uric acid (SUA) target of <6 mg/dL, as recommended by the 2020 American College of Rheumatology guideline 1. For acute gout attacks, the treatment options include NSAIDs, colchicine, or oral corticosteroids, with the choice of drug based on the presence of contraindications, patient's previous experience, and the number and type of joints involved, as suggested by the 2017 EULAR evidence-based recommendations 1. Some key points to consider in gout treatment include:

• Lifestyle modifications, such as weight loss, limiting alcohol intake, and avoiding high-purine foods, can help reduce the frequency of gout attacks, as recommended by the 2017 American College of Physicians guideline 1.
• Urate-lowering therapy should be considered for patients with frequent attacks, tophi, joint damage, or kidney stones, and should be continued indefinitely to maintain SUA levels below 6 mg/dL, as recommended by the 2020 American College of Rheumatology guideline 1.
• During the first few months of ULT, low-dose colchicine or an NSAID may be prescribed to prevent flares triggered by changing uric acid levels, as suggested by the 2017 EULAR evidence-based recommendations 1.
• The choice of ULT should be based on the patient's kidney function, with allopurinol being the preferred first-line option for patients with normal kidney function, and febuxostat or a uricosuric being considered for patients with renal impairment, as recommended by the 2020 American College of Rheumatology guideline 1.

From the FDA Drug Label

The efficacy of KRYSTEXXA was studied in adult patients with chronic gout refractory to conventional therapy in two replicate, multicenter, randomized, double-blind, placebo-controlled studies of six months duration: Trial 1 and Trial 2. Patients were randomized to receive KRYSTEXXA 8 mg every 2 weeks or every 4 weeks or placebo in a 2:2:1 ratio Studies were stratified for the presence of tophi. The primary endpoint in both trials was the proportion of patients who achieved plasma uric acid (PUA) less than 6 mg/dL for at least 80% of the time during Month 3 and Month 6.

Gout Treatment: Pegloticase (IV) is effective in lowering uric acid levels in adult patients with chronic gout refractory to conventional therapy.

• The recommended dose is 8 mg every 2 weeks.
• The primary endpoint of achieving plasma uric acid less than 6 mg/dL for at least 80% of the time during Month 3 and Month 6 was met in a greater proportion of patients treated with pegloticase every 2 weeks compared to placebo 2.
• Indomethacin (PO) is also effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis 3.

From the Research

Gout Treatment Overview

• Gout is a common form of acute inflammatory arthritis caused by the deposition of monosodium urate crystals within the synovium of joints, leading to severe pain and reduced quality of life for patients 4.
• The treatment of gout includes both acute flares of gout and urate-lowering therapy, with a focus on a treat-to-target strategy to prevent gout flares 4, 5, 6.

Acute Gout Flare Treatment

• Standard pharmacotherapies for gout flares include colchicine, NSAIDs, and oral or intramuscular corticosteroids, with IL-1 inhibitors as an option for flare refractory to standard therapies 4, 5, 6.
• Colchicine is a drug with a narrow therapeutic-toxicity window, and co-prescription with strong CYP3A4 or P-glycoprotein inhibitors can greatly modify its pharmacokinetics and should be avoided 7.
• Canakinumab appears to be a good alternative for patients with contraindications to colchicine, NSAIDs, and corticosteroids 7.

Urate-Lowering Therapy

• Urate-lowering therapies aim to prevent gout flares, with an emphasis on a treat-to-target strategy to reach the target serum uric acid level 4, 5, 6.
• Initial treatments include allopurinol and febuxostat, with uricosuric agents such as probenecid, sulfinpyrazone, and benzbromarone as adjuncts 4, 5, 6, 8.
• Allopurinol, febuxostat, and pegloticase are all effective at lowering serum urate compared to placebo, with febuxostat (≥ 80 mg) being more effective at lowering serum urate than allopurinol 8.
• For patients with renal impairment, some authors recommend adjusting the allopurinol maximum dosage to creatinine clearance, and switching to febuxostat if the urate target cannot be achieved 7.

Emerging Therapies and Personalization of Treatment

• There are emerging therapies in development for the treatment of gout, including novel uricosurics such as verinurad and arhalofenate 5.
• The treatment of gout is becoming increasingly personalized, with adjustments made based on comorbidities such as chronic kidney disease and ischemic heart disease, as well as patient preference 4.